The team has vast research history on studying different already established oncogenes that are potential targets for cancer treatment.

TKs (tyrosine kinases) are probably the mostly explored molecules in targeted therapies. We have been studying the response of different cancer types to TK inhibitors already in the clinics, finding new strategies to boost their response (doi: 10.7150/thno.17154).

Examples of new molecular targets are MCTs, Brachyury, RKIP, HOXA9 and WNT proteins that may be targeted in cancer. Monocarboxylate transporters (MCTs) are key molecules in the maintenance of the main metabolic phenotype of cancer cells and are overexpressed in a variety of malignancies. Our studies on MCTs using patient samples and cancer models (doi: 10.1093/neuonc/nos298) contributed to the recognition of MCT1 as target in cancer, which motivated the launching of clinical trials with the MCT1 inhibitor AZD3956 (NCT01791595). In glioblastoma (GBM), we identified HOXA9 as a novel biomarker of poor prognosis in patients, and outlined the critical HOXA9-driven pathways conferring a highly aggressive phenotype and resistance to chemotherapy (doi: 10.18632/oncotarget.3150). We also explored the HOXA9-target genes, of which WNT6 was establishment as a critical oncogene for GBM patients (doi: 10.7150/thno.25025 and International Patent WO/2019/207512A2). Other novel prognostic biomarkers in GBM are Cadherin-3 (doi: 10.1002/1878-0261.13162) and the long non-coding RNA HOTAIR (doi: 10.18632/oncotarget.24597), constituting also novel therapeutic targets. Another key molecule is Brachyury, a crucial development gene that showed to behave as oncogene in different cancer types (doi: 10.1172/JCI38379), leading these studies to further vaccine developments. In GBM, this gene showed a distinct role as tumor suppressor and impacted temozolomide response (doi: 10.1007/s13311-020-00911-9). Many of these biomarkers play a critical role in the crosstalk between malignant and non-malignant cells (e.g. endothelial cells, fibroblasts and immune cells) within the tumour microenvironment.

We have been exploiting these interactions for therapeutic purposes, namely to boost response to novel immunotherapeutic agents (doi.org/10.1038/s41585-019-0263-6). We have also been developing and testing new synthetic molecules for cancer therapy (DOI: 10.1016/j.ejmech.2018.07.058). An example of success is the family of molecules described in the International Patent – WO/2020/261242, that has very promising anticancer activity in poor prognosis cancers, accompanied by a good safety profile, and a novel mechanism of action.